| Author: | Li, Mengheng |
| Title: | A study of the bone protective effects of Tradition Chinese Medicine towards postmenopausal osteoporosis through mass spectrometry-based untargeted metabolomics |
| Advisors: | Mok, Kam-wah Daniel (ABCT) |
| Degree: | Ph.D. |
| Year: | 2023 |
| Subject: | Osteoporosis Osteoporosis in women Medicine, Chinese Hong Kong Polytechnic University -- Dissertations |
| Department: | Department of Applied Biology and Chemical Technology |
| Pages: | xiii, 239 pages : color illustrations |
| Language: | English |
| Abstract: | With the ageing of populations the prevalence of osteoporosis is increasing worldwide and become a serious health issue and economic burden, especially for postmenopausal women. Current medical treatments for postmenopausal osteoporosis, including bisphosphonates, calcium supplement, hormone replacement therapy, and selective estrogen receptor modulators, have been reported to accompany with different degrees of adverse effects, such as breast cancer, endometrial cancer, and cardiovascular diseases. Traditional Chinese medicine (TCM) is a promising alternative approach for managing bone health. However, since TCM is mainly based on empirical clinical experiences accumulated in China and short of the support of modern scientific evidence, the development and popularization of TCM worldwide are severely restricted. Metabolomics is a powerful technique for assessing holistic metabolic alterations caused by interventions. By taking advantages of the information provided by metabolomics, TCM researchers can comprehensively evaluate the therapeutic efficiency, action mechanisms, and safety issue of TCM intervention in vitro or in vivo. Herein, the objective of this dissertation is to use mass spectroscopy-based untargeted metabolomics for assessments of TCM treatment of postmenopausal osteoporosis. The bone protective effects of TCM Sambucus Williamsii Ramulus (SWR), Danggui Buxue Tang (DBT), and Ligustri Lucidi Fructus (LLF) were examined. The first herb studied was the lignan-rich fraction of SWR extract. Serum metabolomics results showed the recovery of the abnormal lipid metabolism (including fatty acids, LysoPCs, and acylcarnitines) and amino acids profile (including methionine metabolism, tryptophan metabolism and BCAAs) by SWR intervention. Moreover, SWR intervention also promoted the antioxidative power of ovariectomized rats, which might be related to its bone protective effects. Our data also supported that gut microbiota might serve as a key factor in facilitating SWR to achieve its bone protective effects. The second TCM studied was DBT, a renowned TCM formula, good for ladies. The bone protective effects of DBT on ovariectomized rats were examined on OVX rats with estrogen supplementation as positive control. There were some common pathways that were regulated by both DBT and estrogen supplementation in the ovariectomized rats, including serum glucocorticoids level, cholesterol level, 5-HETE level, and kynurenine pathway. The overall bile acids level was regulated by estrogen supplementation which helped to maintain bone health and normal cholesterol level. However, DBT intervention only restored the increased secondary bile acids level in ovariectomized rats. This suggested that DBT might regulate the cholesterol level through other metabolic pathway instead of bile acids profile as estrogen supplementation. The third herb studied was LLF, its bone protective effects in aged female rats were examined with high calcium supplementation as positive control. Significant downregulation of 12-HETE and 15-HETE was observed in LLF-treated rats, which indicated activity of lipoxygenases was suppressed by LLF intervention. It is the first report of possible involvement of lipoxygenases in the bone protective effects of LLF. Lipoxygenases also help to have a deep understanding of the modulation of PTH level and RANKL pathway by LLF. Upregulated bile acids profile observed in rats with high calcium supplementation was not only responsible for the bone protective effects of high calcium supplementation, but also contributed to coronary artery calcification. Besides, upregulated acylcarnitines profile was also observed in rats with high calcium supplementation, and it was closely associated with cardiovascular diseases. In summary, this metabolomics study showed that LLF with medium calcium supplementation could achieve comparable bone protective effects to high calcium supplementation, but without the adverse effects accompanied with high calcium supplementation. Hence, LLF with normal dietary calcium intake may serve as a better option for management of postmenopausal osteoporosis. In summary, the study reported here provided evidence that untargeted metabolomics is a powerful and promising approach for holistic assessment of the metabolic profile and discovery of novel biomarkers and pathways for elaborating the working mechanisms of TCM. However, metabolomics study conducted on serum alone also has limitation, because serum only reflects the metabolites in circulation. The actions of gut microbiota are poorly represented by the metabolites in serum, but our results suggested that gut microbiota could be involved in the working mechanism of SWR and DBT. Thus, integrating metabolomics studies of variety of organs and biosamples would definitely broaden the metabolic spectra and provide a more comprehensive view to elucidate the working mechanisms of TCM. |
| Rights: | All rights reserved |
| Access: | open access |
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